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INTRODUCTION: The epidemiological and clinical characteristics of acute poisoning with liquid laundry detergent capsules have been comprehensively reported. However, studies of laboratory test results in these exposures are uncommon. This study analyzed the impact of the ingestion of liquid laundry detergent capsules on admission laboratory tests in paediatric patients. METHODS: This retrospective study was conducted in the clinical toxicology unit of a paediatric poison centre between 2015 and 2021. Paediatric patients (less than 18 years of age) who ingested liquid laundry detergent capsules were included. The relationship between the European Association of Poisons Centers and Clinical Toxicologists/European Commission/International Programme on Chemical Safety Poisoning Severity Score and admission laboratory test results was assessed using Fisher's exact test or analysis of variance. RESULTS: A total of 156 patients were included in the study. A considerable proportion of patients presented with leucocytosis, acidosis, hyperlactataemia or base deficit. The median values of white blood cell count (P = 0.042), pH (P = 0.022), and base excess (P = 0.013) were significantly different among the Poisoning Severity Score groups. Hyperlactataemia was strongly associated with the Poisoning Severity Score (P = 0.003). DISCUSSION: Leucocytosis is a non-specific marker of severity following ingestion of liquid laundry detergent capsules. The incidence of metabolic acidosis and hyperlactataemia was higher in this study than in previous reports, but these metabolic features were not related to the severity of exposure. The exact mechanisms of toxicity are not yet known, but the high concentration of non-ionic and anionic surfactants, as well as propylene glycol and ethanol, in the capsule are likely contributing factors. CONCLUSIONS: Pediatric patients who ingest liquid laundry detergent capsules may develop leucocytosis, metabolic acidosis, hyperlactataemia, and a base deficit.
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Detergentes , Intoxicación , Humanos , Estudios Retrospectivos , Detergentes/envenenamiento , Femenino , Masculino , Preescolar , Niño , Lactante , Intoxicación/epidemiología , Intoxicación/diagnóstico , Intoxicación/sangre , Rumanía/epidemiología , Adolescente , Cápsulas , Índice de Severidad de la Enfermedad , Centros de Control de Intoxicaciones/estadística & datos numéricos , Leucocitosis/inducido químicamente , Leucocitosis/epidemiología , Leucocitosis/sangreRESUMEN
The Brazilian Amazon is home to a rich fauna of scorpion species of medical importance, some of them still poorly characterized regarding their biological actions and range of clinical symptoms after envenoming. The Amazonian scorpion species Tityus strandi and Tityus dinizi constitute some of the scorpions in this group, with few studies in the literature regarding their systemic repercussions. In the present study, we characterized the clinical, inflammatory, and histopathological manifestations of T. strandi and T. dinizi envenoming in a murine model using Balb/c mice. The results show a robust clinical response based on clinical score, hyperglycemia, leukocytosis, increased cytokines, and histopathological changes in the kidneys and lungs. Tityus strandi envenomed mice presented more prominent clinical manifestations when compared to Tityus dinizi, pointing to the relevance of this species in the medical scenario, with both species inducing hyperglycemia, leukocytosis, increased cytokine production in the peritoneal lavage, increased inflammatory infiltrate in the lungs, and acute tubular necrosis after T. strandi envenoming. The results presented in this research can help to understand the systemic manifestations of scorpion accidents in humans caused by the target species of the study and point out therapeutic strategies in cases of scorpionism in remote regions of the Amazon.
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Ratones Endogámicos BALB C , Picaduras de Escorpión , Venenos de Escorpión , Escorpiones , Animales , Venenos de Escorpión/toxicidad , Ratones , Modelos Animales de Enfermedad , Citocinas/metabolismo , Brasil , Leucocitosis/inducido químicamente , Pulmón/patología , Pulmón/efectos de los fármacos , Masculino , Riñón/patología , Riñón/efectos de los fármacos , FemeninoRESUMEN
OBJECTIVE: The remarkable effect of arsenic trioxide (ATO) was verified, but side effects are generally observed in acute promyelocytic leukemia (APL) patients, especially leukocytosis and hepatotoxicity. Our aims are to study predictors and reduce ATO-induced side effects without inhibiting efficacy. METHODS: Sulfhydryl in ATO-treated APL patients was detected by the Spectra Max M5 microplate reader. And patients were divided into high and low sulfhydryl groups according to median sulfhydryl concentration. The onset time of leukocytosis and the peak value of WBC were compared . Correlations between hepatotoxicity indicators and sulfhydryl concentrations were analysed. RESULTS: The concentration of sulfhydryl before treatment was significantly higher in the high sulfhydryl group. Leukocytosis ((7.0 ± 5.5) vs. (14.6 ± 8.5) day) and the peak value of WBC occurred earlier in the low sulfhydryl group ((10.8 ± 5.9) vs. (19.3 ± 5.5) day) than in the high group, and the peak value was significantly lower in the low sulfhydryl group ((24.04 ± 15.05) × 109/L) than in the high group ((42.95 ± 25.57) × 109/L). The elevated liver enzymes were smaller in the higher sulfhydryl group between time points before treatment and the treatment one week later (ΔALT 66.57 vs. 9.85â U/L, ΔAST 59.52 vs. 17.76â U/L), as between time points before treatment and peak value. There was a negative correlation between sulfhydryl and elevated liver enzymes. CONCLUSIONS: Higher sulfhydryl compounds contribute to ameliorating ATO-induced leukocytosis and hepatotoxicity in APL patients. The low sulfhydryl before treatment can advance the onset of leukocytosis. For patients with higher sulfhydryl in the early stage, close monitoring of liver enzymes is warranted instead of prophylactic applying any hepatoprotective intervention, to maintain ATO efficacy.
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Arsenicales , Enfermedad Hepática Inducida por Sustancias y Drogas , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Leucemia Promielocítica Aguda , Humanos , Trióxido de Arsénico/efectos adversos , Leucemia Promielocítica Aguda/tratamiento farmacológico , Leucocitosis/inducido químicamente , Compuestos de Sulfhidrilo/efectos adversos , Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Enfermedad Hepática Inducida por Sustancias y Drogas/tratamiento farmacológico , Óxidos/efectos adversos , TretinoinaRESUMEN
INTRODUCTION: Neuroleptic malignant syndrome (NMS) is uncommon, with an incidence of 0.01%-3.23%, and is associated with the use of drugs that intervene with dopamine, causing hyperthermia, muscular rigidity, confusion, autonomic instability and death. CASE REPORT: A 35-year-old man with a history of catatonia, refractory epilepsy and functional impairment, required frequent changes in his anticonvulsant and antipsychotic treatment, due to adverse effects. During 2019, in the month of July, clozapine was changed to amisulpride, in September he developed fever, muscle stiffness, stupor, diaphoresis and tachypnea over a two-week period; paraclinical tests showed elevated creatine phosphokinase (CPK) and leukocytosis, so NMS was considered. The antipsychotic was withdrawn and he was treated with bromocriptine and biperiden, with a good response. Ten days after discharge, he began treatment with olanzapine, which generated a similar episode to the one described in December, with subsequent management and resolution. DISCUSSION: The diagnosis is based on the use of drugs that alter dopamine levels, plus altered state of consciousness, fever, autonomic instability and paraclinical tests showing leukocytosis and elevated CPK. Differential diagnoses must be ruled out. Early diagnosis generally leads to total remission, although some patients will suffer complications, long-term sequelae or recurrences. The recurrence in this case derived from the early reintroduction of the neuroleptic after the first episode. Treatment should be individualised according to severity to avoid mortality. CONCLUSIONS: Atypical antipsychotics are rarely suspected of generating NMS. Moreover, the time to reintroduction after an episode must also be taken into account.
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Antipsicóticos , Síndrome Neuroléptico Maligno , Masculino , Humanos , Adulto , Antipsicóticos/efectos adversos , Síndrome Neuroléptico Maligno/diagnóstico , Síndrome Neuroléptico Maligno/etiología , Dopamina/uso terapéutico , Leucocitosis/inducido químicamente , Leucocitosis/complicaciones , Leucocitosis/tratamiento farmacológico , Amisulprida/efectos adversosRESUMEN
BACKGROUND: Neutropenia is a noteworthy side effect of clozapine, which might warrant this drugs' discontinuance for safety. Studies have revealed that the risk of neutropenia increases with concurrent administration of valproate, but the evidence was limited. Conversely, lithium may have an ameliorating effect on clozapine-induced neutropenia. This study explored the effects of valproate and lithium on white blood cell counts in patients treated with clozapine. METHODS: We retrospectively investigated the electronic medical records from one tertiary psychiatric hospital in Taiwan and enrolled patients discharged between January 1, 2006, and December 31, 2017, with clozapine prescriptions. We scrutinized their demographic data, medications, and hematological results at discharge and during follow-up outpatient clinic visits over the subsequent 3 years. Patients were classified into four groups: clozapine only (CLO), clozapine and valproate (CLO + VAL), clozapine and lithium (CLO + Li), and clozapine, valproate, and lithium (CLO + VAL + Li). We also identified hematological events (neutropenia or leukocytosis) of these patients during outpatient follow-ups. RESULTS: Of the included 1084 patients, 55(5.1%) developed neutropenia. Concurrent valproate use (odds ratio [OR] = 3.49) and older age (p = .007) were identified as risk factors. Moreover, 453 (41.79%) patients developed leukocytosis. Younger age; male sex; and concurrent use of lithium (OR = 3.39, p < .001), clozapine daily dosage, and benzodiazepines were the risk factors for leukocytosis. CONCLUSION: Concurrent valproate use and older age are associated with the development of neutropenia in patients treated with clozapine. Concurrent lithium usage, younger age, male sex, and concurrent benzodiazepine use might be related to leukocytosis.
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Antipsicóticos , Clozapina , Neutropenia , Humanos , Masculino , Clozapina/efectos adversos , Ácido Valproico/efectos adversos , Litio/uso terapéutico , Estudios Retrospectivos , Antipsicóticos/efectos adversos , Leucocitosis/inducido químicamente , Leucocitosis/tratamiento farmacológico , Neutropenia/inducido químicamente , Benzodiazepinas/efectos adversosRESUMEN
Immune checkpoint inhibitors (ICIs) have proven clinical benefits in various advanced cancers. However, despite their significant therapeutic efficacy, ICIs induce immune-related adverse events. Among these events, autoimmune meningoencephalitis often has severe effects on patients' outcomes, but its specific clinical features are still unclear. Here, we report two cases of ICI-associated meningoencephalitis with elevated interleukin-6 (IL-6) levels in the cerebrospinal fluid (CSF). A 47-year-old woman (Case 1) with renal cell carcinoma developed severe headache after a seventh nivolumab administration. A neurological examination revealed jolt accentuation signs and hyperreflexia in all extremities. CSF analysis revealed a high IL-6 value (6,620 pg/mL) with marked pleocytosis. A 70-year-old woman (Case 2) who received an initial administration of nivolumab plus ipilimumab for renal cell carcinoma developed alterations of consciousness. She presented with impaired consciousness, neck stiffness, and hyperreflexia in all extremities. CSF analysis demonstrated a high IL-6 value (49.3 pg/mL) with mild pleocytosis. Both patients were treated with steroid pulse therapy (methylprednisolone 1,000 mg/day, 3 days), followed by the administration of oral predonisolone. The symptoms and laboratory findings improved in both cases. CSF IL-6 values were proportional to the severity of meningoencephalitis and other clinical parameters. These findings may help elucidate the mechanisms of central nervous system complications that are caused by ICIs.
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Carcinoma de Células Renales , Neoplasias Renales , Meningoencefalitis , Anciano , Carcinoma de Células Renales/tratamiento farmacológico , Femenino , Humanos , Inhibidores de Puntos de Control Inmunológico , Interleucina-6 , Ipilimumab/efectos adversos , Neoplasias Renales/tratamiento farmacológico , Leucocitosis/inducido químicamente , Meningoencefalitis/líquido cefalorraquídeo , Meningoencefalitis/inducido químicamente , Meningoencefalitis/diagnóstico , Metilprednisolona , Persona de Mediana Edad , Nivolumab/efectos adversos , Reflejo AnormalRESUMEN
The development of myeloid leukocytosis in leukemia patients during antileukemic treatment requires a differential diagnosis between myeloid leukemoid reaction and leukemia progression. We herein report the case of an 80-year-old Japanese man with chronic myelomonocytic leukemia (CMML) who developed marked myeloid leukocytosis (36.3 × 109/L) with 32.5% monocytes and 48% neutrophils about 4 weeks after the initial 5-azacitidine (AZA) treatment. The leukocytosis was unlikely to be attributed to infection and adverse drug reaction. As it resolved in a few days without any interventions, the transient myeloid leukocytosis was confirmed to be a myeloid leukemoid reaction. After four cycles of AZA treatment, leukemic blasts in the bone marrow decreased and the patient became transfusion-independent. Interestingly, levels of serum G-CSF showed a similar trend to the myeloid leukocytosis, while those of serum GM-CSF and IL-17 were undetectable throughout the clinical course, suggesting that a differentiation response to AZA treatment might lead to the myeloid leukemoid reaction. Our case implies that a marked but transient myeloid leukemoid reaction mimicking CMML progression can develop during AZA treatment, which requires careful clinical monitoring and differential diagnosis.
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Leucemia Mielomonocítica Crónica , Leucemia Mielomonocítica Juvenil , Reacción Leucemoide , Masculino , Humanos , Anciano de 80 o más Años , Leucemia Mielomonocítica Crónica/tratamiento farmacológico , Azacitidina/efectos adversos , Reacción Leucemoide/inducido químicamente , Reacción Leucemoide/diagnóstico , Leucocitosis/inducido químicamente , Leucemia Mielomonocítica Juvenil/tratamiento farmacológicoRESUMEN
BACKGROUND AND OBJECTIVES: Corticosteroids are commonly used in the treatment of hospitalized patients with COVID-19. The goals of the present study were to compare the efficacy and safety of different doses of dexamethasone in the treatment of patients with a diagnosis of moderate to severe COVID-19. METHODS: Hospitalized patients with a diagnosis of moderate to severe COVID-19 were assigned to intravenous low-dose (8 mg once daily), intermediate-dose (8 mg twice daily) or high-dose (8 mg thrice daily) dexamethasone for up to 10 days or until hospital discharge. Clinical response, 60-day survival and adverse effects were the main outcomes of the study. RESULTS: In the competing risk survival analysis, patients in the low-dose group had a higher clinical response than the high-dose group when considering death as a competing risk (HR = 2.03, 95% CI: 1.23-3.33, p = 0.03). Also, the survival was significantly longer in the low-dose group than the high-dose group (HR = 0.36, 95% CI = 0.15-0.83, p = 0.02). Leukocytosis and hyperglycemia were the most common side effects of dexamethasone. Although the incidence was not significantly different between the groups, some adverse effects were numerically higher in the intermediate-dose and high-dose groups than in the low-dose group. CONCLUSIONS: Higher doses of dexamethasone not only failed to improve efficacy but also resulted in an increase in the number of adverse events and worsen survival in hospitalized patients with moderate to severe COVID-19 compared to the low-dose dexamethasone. (IRCT20100228003449N31).
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Antiinflamatorios/administración & dosificación , Antiinflamatorios/uso terapéutico , Tratamiento Farmacológico de COVID-19 , Dexametasona/administración & dosificación , Dexametasona/uso terapéutico , Adulto , Anciano , Antiinflamatorios/efectos adversos , Dexametasona/efectos adversos , Relación Dosis-Respuesta a Droga , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/epidemiología , Femenino , Humanos , Hiperglucemia/inducido químicamente , Incidencia , Leucocitosis/inducido químicamente , Masculino , Persona de Mediana Edad , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
Caustic chemicals are widely distributed in our environment. Exposure to caustic agents is a lifelong problem associated with severe tissue and mucous membrane injuries. In pediatrics, corrosive exposure is the most common cause of nonpharmaceutical exposure presenting to poison control centers. Therefore, this study evaluated the role of the Pediatric Early Warning System (PEWS) and Drooling Reluctance Oropharynx Others Leukocytosis (DROOL) scores as early in-hospital outcome predictors following corrosive ingestion. The current study was a two-center, retrospective, cross-sectional study carried out among pediatric patients diagnosed with acute caustic ingestion during the past 4 years. Most exposure occurred accidentally among boys (59.4%) living in rural areas (51.9%) of preschool age (50% were 2-4 years old). Residence, body temperature, respiratory rate, vomiting, skin and mucosal burns, retrosternal pain, respiratory distress, Oxygen (O2) saturation, Glasgow Coma Scale score, HCO3 level, total bilirubin level, anemia, leukocytosis, and presence of free peritoneal fluid were significant predictors of esophageal injuries (p < 0.05). DROOL and PEWS scoring were the most significant predictors of esophageal injuries with worthy predictive power, where odds ratio (95% confidence interval (CI)) was 1.76 (0.97-3.17) and 0.47 (0.21-0.99) for PEWS and DROOL, respectively. At a cutoff of < 6.5, the DROOL score could predict esophageal injuries excellently, with AUC = 0.931; sensitivity, 91.7%; specificity, 72.5%; and overall accuracy, 91.3%. At a cutoff of > 6.5, PEWS could significantly predict unfavorable outcomes, with AUC = 0.893; sensitivity, 94.4%; specificity, 71.9%; and overall accuracy, 89.3%. However, PEWS better predicted the need for admittance to the intensive care unit (ICU). Pediatric Early Warning System (PEWS) and Drooling Reluctance Oropharynx Others Leukocytosis (DROOL) are potentially useful accurate scorings that could predict the esophageal injuries and ICU admission following corrosive ingestion in pediatrics.
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Cáusticos , Pediatría , Sialorrea , Niño , Preescolar , Estudios Transversales , Ingestión de Alimentos , Humanos , Lactante , Leucocitosis/inducido químicamente , Masculino , Orofaringe , Pronóstico , Curva ROC , Estudios RetrospectivosRESUMEN
BACKGROUND AND OBJECTIVES: Clozapine is the only antipsychotic approved for treatment-resistant schizophrenia. Despite its superior efficacy profile as compared with other antipsychotics, clozapine remains underutilized. Clozapine monitoring systems clearly describe the proposed management of clozapine-induced neutropenia; however, no specific mention is made of how to interpret neutrophilic leukocytosis, despite that being a relatively frequent finding. Prescribers unfamiliar with this molecule may misjudge its clinical significance, potentially leading to untimely treatment interruption. Here, we systematically review the literature on the risk of neutrophilic leukocytosis during clozapine treatment, and describe eight additional cases among our patient cohort. MATERIALS AND METHODS: We performed a systematic review of the literature on PubMed and Embase using the PRISMA 2020 guidelines, and selected all original reports describing either (1) the prevalence of neutrophilic leukocytosis during clozapine treatment, or (2) the clinical significance of neutrophilic leukocytosis. We described eight additional cases of neutrophilic leukocytosis during clozapine treatment while attending an outpatient psychiatric clinic. RESULTS: Our research ultimately yielded the selection of 13 articles included in this systematic review. The case series highlighted the presence of stable and clinically unremarkable neutrophilia during a follow-up ranging from one to ten years. CONCLUSIONS: Existing evidence indicates that leukocytosis associated with clozapine treatment can be considered as an asymptomatic and benign condition, suggesting that no change in clozapine treatment is needed upon its detection.
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Antipsicóticos , Clozapina , Esquizofrenia , Antipsicóticos/efectos adversos , Clozapina/efectos adversos , Humanos , Leucocitosis/inducido químicamente , Leucocitosis/tratamiento farmacológico , Prevalencia , Esquizofrenia/tratamiento farmacológicoRESUMEN
Whooping cough is caused by Bordetella pertussis that releases pertussis toxin (PT) which comprises enzyme A-subunit PTS1 and binding/transport B-subunit. After receptor-mediated endocytosis, PT reaches the endoplasmic reticulum from where unfolded PTS1 is transported to the cytosol. PTS1 ADP-ribosylates G-protein α-subunits resulting in increased cAMP signaling. Here, a role of target cell chaperones Hsp90, Hsp70, cyclophilins and FK506-binding proteins for cytosolic PTS1-uptake is demonstrated. PTS1 specifically and directly interacts with chaperones in vitro and in cells. Specific pharmacological chaperone inhibition protects CHO-K1, human primary airway basal cells and a fully differentiated airway epithelium from PT-intoxication by reducing intracellular PTS1-amounts without affecting cell binding or enzyme activity. PT is internalized by human airway epithelium secretory but not ciliated cells and leads to increase of apical surface liquid. Cyclophilin-inhibitors reduced leukocytosis in infant mouse model of pertussis, indicating their promising potential for developing novel therapeutic strategies against whooping cough.
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Bordetella pertussis/enzimología , Sistemas de Liberación de Medicamentos , Inhibidores Enzimáticos/farmacología , Células Epiteliales/metabolismo , Leucocitosis , Chaperonas Moleculares , Toxina del Pertussis/toxicidad , Animales , Bordetella pertussis/metabolismo , Bordetella pertussis/patogenicidad , Células CHO , Cricetulus , Células Epiteliales/microbiología , Células HEK293 , Humanos , Leucocitosis/inducido químicamente , Leucocitosis/tratamiento farmacológico , Leucocitosis/metabolismo , Ratones , Chaperonas Moleculares/antagonistas & inhibidores , Chaperonas Moleculares/genética , Chaperonas Moleculares/metabolismoRESUMEN
INTRODUCTION: Sweet Syndrome, also known as acute febrile neutrophilic dermatosis, is a rare inflammatory disease characterized by the sudden emergence of painful, edematous, and erythematous papules, plaques, or nodules on the skin, which usually fully responsive to systemic corticosteroids. Skin lesions are often accompanied by fever and leukocytosis. Here we present a case of Sweet Syndrome caused by pemetrexed in metastatic lung adenocarcinoma. CASE REPORT: A 52-year-old patient with metastatic lung adenocarcinoma received multiple lines of chemotherapy. The patient presented with extensive skin lesions after performing of pemetrexed chemotherapy. He had a fever and elevations in blood levels of C-reactive protein (CRP), sedimentation, leucocytes, and neutrophils. Neutrophil predominant perivascular and interstitial dermatitis, focal micropustule formation, and severe neutrophilic dermatosis were reported in skin biopsy. Topical steroid and oral antihistamine treatment were started as initial treatment.Discussion and conclusions: Cutaneous side effects related to pemetrexed are often reported as 'skin rash,' which is a non-specific term. Therefore, the diagnosis of Sweet Syndrome must be confirmed by skin biopsy. It is essential to exclude the presence of an infection and medication history. Recovery in drug-induced Sweet Syndrome occurs after the drug that caused it was discontinued. Systemic corticosteroids are the first-line treatment for most cases.
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Pemetrexed/efectos adversos , Síndrome de Sweet/inducido químicamente , Biopsia , Femenino , Fiebre/inducido químicamente , Humanos , Leucocitosis/inducido químicamente , Persona de Mediana Edad , Neutrófilos/citología , Piel/patologíaRESUMEN
INTRODUCTION: Methotrexate-induced pneumonitis is a rare but potentially fatal side effect. It is a diagnosis of exclusion. There are early and late forms and different cell patterns in the bronchoalveolar lavage (BAL). CASE REPORT: We present a case of acute interstitial lung disease in a 54-year-old patient who had been taking methotrexate for a year and a half for rheumatoid arthritis. After excluding other causes and based on the diagnostic criteria of Searles and McKendry, we could reasonably identify methotrexate as the cause of the lung disease. It was of late onset and the BAL showed neutrophilia and eosinophilia. CONCLUSION: Methotrexate-induced pneumonitis is a diagnosis of exclusion. A late onset combined with the predominance of neutrophils and eosinophils in BAL is rare in the literature, demonstrating the wide heterogeneity of methotrexate-related interstitial lung disease.
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Eosinofilia/inducido químicamente , Leucocitosis/inducido químicamente , Enfermedades Pulmonares Intersticiales/inducido químicamente , Metotrexato/efectos adversos , Enfermedad Aguda , Líquido del Lavado Bronquioalveolar , Eosinofilia/diagnóstico , Eosinofilia/patología , Femenino , Humanos , Leucocitosis/complicaciones , Leucocitosis/diagnóstico , Enfermedades Pulmonares Intersticiales/complicaciones , Enfermedades Pulmonares Intersticiales/diagnóstico , Enfermedades Pulmonares Intersticiales/patología , Persona de Mediana Edad , Neutrófilos/patología , Fiebre Reumática/tratamiento farmacológico , Fiebre Reumática/patología , Tomografía Computarizada por Rayos XRESUMEN
BACKGROUND: Tofersen is an antisense oligonucleotide that mediates the degradation of superoxide dismutase 1 (SOD1) messenger RNA to reduce SOD1 protein synthesis. Intrathecal administration of tofersen is being studied for the treatment of amyotrophic lateral sclerosis (ALS) due to SOD1 mutations. METHODS: We conducted a phase 1-2 ascending-dose trial evaluating tofersen in adults with ALS due to SOD1 mutations. In each dose cohort (20, 40, 60, or 100 mg), participants were randomly assigned in a 3:1 ratio to receive five doses of tofersen or placebo, administered intrathecally for 12 weeks. The primary outcomes were safety and pharmacokinetics. The secondary outcome was the change from baseline in the cerebrospinal fluid (CSF) SOD1 concentration at day 85. Clinical function and vital capacity were measured. RESULTS: A total of 50 participants underwent randomization and were included in the analyses; 48 participants received all five planned doses. Lumbar puncture-related adverse events were observed in most participants. Elevations in CSF white-cell count and protein were reported as adverse events in 4 and 5 participants, respectively, who received tofersen. Among participants who received tofersen, one died from pulmonary embolus on day 137, and one from respiratory failure on day 152; one participant in the placebo group died from respiratory failure on day 52. The difference at day 85 in the change from baseline in the CSF SOD1 concentration between the tofersen groups and the placebo group was 2 percentage points (95% confidence interval [CI], -18 to 27) for the 20-mg dose, -25 percentage points (95% CI, -40 to -5) for the 40-mg dose, -19 percentage points (95% CI, -35 to 2) for the 60-mg dose, and -33 percentage points (95% CI, -47 to -16) for the 100-mg dose. CONCLUSIONS: In adults with ALS due to SOD1 mutations, CSF SOD1 concentrations decreased at the highest concentration of tofersen administered intrathecally over a period of 12 weeks. CSF pleocytosis occurred in some participants receiving tofersen. Lumbar puncture-related adverse events were observed in most participants. (Funded by Biogen; ClinicalTrials.gov number, NCT02623699; EudraCT number, 2015-004098-33.).
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Esclerosis Amiotrófica Lateral/tratamiento farmacológico , Oligonucleótidos Antisentido/administración & dosificación , Oligonucleótidos/administración & dosificación , Superóxido Dismutasa-1/líquido cefalorraquídeo , Adulto , Esclerosis Amiotrófica Lateral/líquido cefalorraquídeo , Esclerosis Amiotrófica Lateral/genética , Progresión de la Enfermedad , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Femenino , Cefalea/inducido químicamente , Humanos , Inyecciones Espinales/efectos adversos , Filamentos Intermedios , Leucocitosis/inducido químicamente , Masculino , Persona de Mediana Edad , Mutación , Oligonucleótidos/efectos adversos , Oligonucleótidos/farmacocinética , Oligonucleótidos Antisentido/efectos adversos , Oligonucleótidos Antisentido/farmacocinética , Superóxido Dismutasa-1/genética , Capacidad VitalRESUMEN
MEDICAL HISTORY AND CLINICAL PRESENTATION: A 66-year-old female patient was admitted to the emergency department following bitter zucchini ingestion. Clinical symptoms were tachycardia, hypotension, somnolence, diarrhea, hematochezia as well as exsiccosis, nausea and emesis. EXAMINATION AND DIAGNOSIS: Laboratory results showed leukocytosis and signs of exsiccosis. Ultrasound revealed thickening of the sigmoid colon wall, interpretable as acute colitis. Poisoning with cucurbitacin containing zucchini was diagnosed. THERAPY: The patient improved after intravenous fluid administration. Hemorrhagic colitis with diarrhea was self limiting. After 2 days, the patient was able to eat again. CONCLUSION: Acute food poisoning due to cucurbitacin - containing pumpkin is rare but can occur in small gardening units in association with higher outside temperatures. Cucurbitacin poisoning has to be taken into account for differential diagnosis in food poisoning. Bitter taste is essential to diagnose cucurbitacin intoxications.
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Cucurbitacinas/efectos adversos , Enfermedades Transmitidas por los Alimentos/diagnóstico , Enfermedades Transmitidas por los Alimentos/etiología , Anciano , Colitis/inducido químicamente , Colon Sigmoide/efectos de los fármacos , Diagnóstico Diferencial , Diarrea/inducido químicamente , Femenino , Hemorragia Gastrointestinal/inducido químicamente , Humanos , Leucocitosis/inducido químicamente , Náusea/inducido químicamente , Ultrasonografía , Vómitos/inducido químicamenteRESUMEN
Non-arteritic anterior ischemic optic neuropathy (NAION) causes a sudden loss of vision and lacks effective treatment. Granulocyte colony-stimulating factor (G-CSF) provides neuroprotection against the experimental optic nerve injuries but also induce leukocytosis upon typical administration. We found synergetic neuroprotective effects of meloxicam and low dose G-CSF without leukocytosis in a rat model of anterior ischemic optic neuropathy (rAION). The WBC counts in the low-dose G-CSF-plus meloxicam-treated group were similar to the sham-operated group. Combination treatment of low-dose G-CSF plus meloxicam preserved RGCs survival and visual function, reduced RGC apoptosis and the macrophages infiltration, and promote more M2 phenotype of macrophage/microglial transition than the low-dose GCSF treatment or the meloxicam treatment. Moreover, the combination treatment induced higher serine/threonine kinase 1 (Akt1) expression. The combination treatment of low-dose G-CSF plus meloxicam lessened the leukocytotic side effect and provided neuroprotective effects via Akt1 activation in the rAION model. This approach provides crucial preclinical information for the development of alternative therapy in AION.
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Factor Estimulante de Colonias de Granulocitos/farmacología , Meloxicam/farmacología , Fármacos Neuroprotectores/farmacología , Neuropatía Óptica Isquémica/tratamiento farmacológico , Animales , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Sinergismo Farmacológico , Quimioterapia Combinada/métodos , Factor Estimulante de Colonias de Granulocitos/uso terapéutico , Humanos , Recuento de Leucocitos , Leucocitosis/inducido químicamente , Leucocitosis/prevención & control , Macrófagos/efectos de los fármacos , Macrófagos/inmunología , Masculino , Meloxicam/uso terapéutico , Fármacos Neuroprotectores/uso terapéutico , Nervio Óptico/efectos de los fármacos , Nervio Óptico/patología , Neuropatía Óptica Isquémica/sangre , Neuropatía Óptica Isquémica/inmunología , Neuropatía Óptica Isquémica/patología , Proteínas Proto-Oncogénicas c-akt/metabolismo , Ratas , Células Ganglionares de la Retina/efectos de los fármacos , Células Ganglionares de la Retina/patología , Transducción de Señal/efectos de los fármacos , Transducción de Señal/inmunologíaRESUMEN
Sulfur mustard (SM) is a vesicant chemical warfare agent. Recent studies reported alleged use of SM by non-state actors in Syria and Iraq. It has been shown that SM induced immunological and hematological complications. The aim of this study was to determine acute toxic effects of SM exposure on hematological parameters. Blood samples from a group of Syrian exposed to SM in 2016 were taken daily during the follow-up of the patients in intensive care unit. Initial leukocytosis was observed in all patients (100%) on the first 48â¯h after exposure. Following leukocytosis, isolated lymphopenia was observed in all patients (100%) between 2nd and 4th days. A decrease in hemoglobin level was noted in five patients (62.5%) between 4th and 5th days. Thrombocytopenia was observed in 75% of patients between 4th and 6th days for mild cases and between 9th and 11th days for severe cases. Three patients (37.5%) developed distinct leucopenia/neutropenia on 11th and 12th days. It was observed that human exposure to high dose of SM has direct toxic effect on hematological cells and bone marrow. New strategies on treatment of SM-induced myelosuppression could reduce the effects of hematological complications and could increase the survival rate in these patients.
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Médula Ósea/efectos de los fármacos , Terrorismo Químico , Sustancias para la Guerra Química/envenenamiento , Leucocitosis/inducido químicamente , Leucopenia/inducido químicamente , Linfopenia/inducido químicamente , Gas Mostaza/envenenamiento , Trombocitopenia/inducido químicamente , Adolescente , Adulto , Biomarcadores/sangre , Médula Ósea/patología , Femenino , Hemoglobinas/metabolismo , Humanos , Leucocitosis/sangre , Leucocitosis/patología , Leucopenia/sangre , Leucopenia/patología , Linfopenia/sangre , Linfopenia/patología , Masculino , Siria , Trombocitopenia/sangre , Trombocitopenia/patología , Adulto JovenRESUMEN
BACKGROUND: Non-traumatic intramural hematomas of the small bowel (IHSB) are rare conditions which occur due to anticoagulant therapy. In this study, we aimed to explain our clinical approach to non-traumatic IHSB due to anticoagulant overdose and to present the long-term outcomes of the cases who were hospitalized. METHODS: Sixteen patients with non-traumatic IHSB were included and their medical records were retrospectively reviewed. RESULTS: Our patients included ten women and six men, with a mean age of 77.5 ± 8.4 (range: 65-95) years. All patients had been using oral anticoagulants (OACs) due to various cardiovascular and cerebral comorbidities. Common complaints at the time of admission included abdominal pain, vomiting and weakness. Ten patients (62%) had anemia, fifteen (94%) had leukocytosis and all patients (100%) had high levels of C-reactive protein (CRP). Abdominal computed tomography (CT) established the final diagnosis of IHSB in all patients. Fourteen patients (87%) were followed up with conservative therapy. Since the clinical course did not improve in two patients (12%), surgery was mandated. The mean duration of hospitalization was 10.25 ± 3.6 days (range: 3-17 days). Mortality occurred in two patients (12%). CONCLUSION: IHSB should be considered in patients presenting with abdominal complaints and increased levels on coagulation tests. The diagnosis should be confirmed by abdominal CT scan, if possible. Accurate and timely diagnosis allows patients to be successfully treated without need for surgery.
Asunto(s)
Anticoagulantes/envenenamiento , Hemorragia Gastrointestinal/inducido químicamente , Hematoma/inducido químicamente , Intestino Delgado/diagnóstico por imagen , Dolor Abdominal/inducido químicamente , Anciano , Anciano de 80 o más Años , Proteína C-Reactiva/metabolismo , Sobredosis de Droga/complicaciones , Sobredosis de Droga/diagnóstico , Sobredosis de Droga/terapia , Femenino , Hemorragia Gastrointestinal/diagnóstico , Hemorragia Gastrointestinal/terapia , Hematoma/diagnóstico , Hematoma/terapia , Humanos , Intestino Delgado/patología , Tiempo de Internación , Leucocitosis/inducido químicamente , Masculino , Estudios Retrospectivos , Tomografía Computarizada por Rayos XRESUMEN
Complement (C) activation can underlie the infusion reactions to liposomes and other nanoparticle-based medicines, a hypersensitivity syndrome that can be partially reproduced in animal models. However, the sensitivities and manifestations substantially differ in different species, and C activation may not be the only cause of pathophysiological changes. In order to map the species variation of C-dependent and -independent pseudoallergy (CARPA/CIPA), here we used known C activators and C activator liposomes to compare their acute hemodynamic, hematological, and biochemical effects in rats. These C activators were cobra venom factor (CVF), zymosan, AmBisome (at 2 doses), its amphotericin B-free vehicle (AmBisombo), and a PEGylated cholesterol-containing liposome (PEG-2000-chol), all having different powers to activate C in rat blood. The pathophysiological endpoints measured were blood pressure, leukocyte and platelet counts, and plasma thromboxane B2, while C activation was assessed by C3 consumption using the Pan-Specific C3 assay. The results showed strong linear correlation between C activation and systemic hypotension, pointing to a causal role of C activation in the hemodynamic changes. The observed thrombocytopenia and leukopenia followed by leukocytosis also correlated with C3 conversion in case of C activators, but not necessarily with C activation by liposomes. These findings are consistent with the double hit hypothesis of hypersensitivity reactions (HSRs), inasmuch as strong C activation can fully account for all symptoms of HSRs, but in case of no-, or weak C activators, the pathophysiological response, if any, is likely to involve other activation pathways.